The role of GAB receptors in the function of adrenal chromaffin cells was studied in situ by autoperfusion of canine adrenal gland. GAB-A receptor agonists increased the resting outflow of catecholamine and met-enkephalin-like peptides in the adrenal venous blood, while GAB-B receptor agonists had no effect. Denervation of the adrenal gland two weeks before the experiment failed to prevent the effect of GAB-A receptor agonists indicating that GAB-A receptors are located on chromaffin cells. When the release of catecholamines and met-enkephalin-like peptides was elicited by electrical stimulation of the splanchnic nerve GAB-A receptor agonists attenuated this increase while GAB-A-receptor antagonists facilitated it. Direct stimulation of GAB-A receptors located on chromaffin cell membranes causes bursts of Cl- channel opening resulting in depolarization of chromaffin cell membranes and thereby facilitating the spontaneous release of neurotransmitters. It is proposed that this type of depolarization involving bursts of Cl- channel opening may obtund the depolarizing effect of nicotinic receptor stimulation. Hence in the adrenal medulla GAB can be viewed as a primary transmitter that modifies the effect of nicotinic receptor stimulation by acting on a different transducer system, presumably the Cl- channel.